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A Study Evaluating the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Participants With Uncontrolled Asthma

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ClinicalTrials.gov Identifier: NCT02099656
Recruitment Status : Completed
First Posted : March 31, 2014
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 26, 2014
First Posted Date  ICMJE March 31, 2014
Last Update Posted Date September 6, 2017
Actual Study Start Date  ICMJE November 6, 2014
Actual Primary Completion Date October 13, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2017)
Relative Change From Baseline in the Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells per Square Millimeter [Cells/mm^2]) [ Time Frame: From Baseline to Week 12 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
Relative change in the number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2) [ Time Frame: From Baseline to Week 12 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2017)
  • Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Surface Area of Basal Lamina (Cells/mm^2) [ Time Frame: From Baseline to Week 12 ]
  • Relative Change From Baseline in the Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2) [ Time Frame: From Baseline to Week 12 ]
  • Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Surface Area of Basal Lamina (Cells/mm^2) [ Time Frame: From Baseline to Week 12 ]
  • Relative Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells per Cubic Millimeter [Cells/mm^3]) [ Time Frame: From Baseline to Week 12 ]
  • Absolute Change From Baseline in Number of Airway Submucosal Eosinophils per Volume of Submucosa (Cells/mm^3) [ Time Frame: From Baseline to Week 12 ]
  • Relative Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3) [ Time Frame: From Baseline to Week 12 ]
  • Absolute Change From Baseline in Number of Airway Epithelial Eosinophils per Volume of Epithelium (Cells/mm^3) [ Time Frame: Form Baseline to Week 12 ]
  • Change From Baseline in Blood Eosinophil Count [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Immunoglobulin E (IgE) Levels [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Serum Periostin Levels [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Chemokine Ligand (CCL)-13 Levels [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in CCL-17 Levels [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Lung Epithelial Cell Chloride Channel Accessory 1 (CLCA1) Gene Expression [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Lung Epithelial Cell SerpinB2 Gene Expression at Week 12 [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Lung Epithelial Cell CCL-26 Gene Expression [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Lung Epithelial Cell Nitric Oxide Synthase 2 (NOS2) Gene Expression [ Time Frame: From Baseline to Week 12 ]
  • Change From Baseline in Lung Epithelial Cell Periostin (POSTN) Gene Expression [ Time Frame: From Baseline to Week 12 ]
  • Relative Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) [ Time Frame: From Baseline to Week 12 ]
  • Relative Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: From Baseline to Week 12 ]
  • Percentage of Participants With Treatment-Emergent Adverse Events [ Time Frame: From Baseline to Week 20 ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Lebrikizumab [ Time Frame: Baseline up to Week 20 (assessed at Baseline, Weeks 8 and 20/dosing termination or early termination) ]
  • Serum Lebrikizumab Concentration at Week 12 [ Time Frame: Predose (Hour 0) at Week 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2014)
  • Relative change in forced expiratory volume in 1 second (FEV1) [ Time Frame: From Baseline to Week 12 ]
  • Incidence of adverse events [ Time Frame: Up to Week 20 ]
  • Absolute change in number of airway submucosal eosinophils per surface area of basal lamina (cells/mm2) [ Time Frame: From Baseline to Week 12 ]
  • Relative change in the number of airway epithelial eosinophils per surface area of basal lamina (cells/mm2) [ Time Frame: From Baseline to Week 12 ]
  • Absolute change in the number of airway epithelial eosinophils per surface area of basal lamina (cells/mm2) [ Time Frame: From Baseline to Week 12 ]
  • Relative change in number of airway submucosal eosinophils per volume of submucosa (cells/mm3) [ Time Frame: From Baseline to Week 12 ]
  • Absolute change in number of airway submucosal eosinophils per volume of submucosa (cells/mm3) [ Time Frame: Form Baseline to Week 12 ]
  • Relative change in number of airway epithelial eosinophils per volume of epithelium (cells/mm3) [ Time Frame: From Baseline to Week 12 ]
  • Absolute change in number of airway epithelial eosinophils per volume of epithelium (cells/mm3) [ Time Frame: From Baseline to Week 12 ]
  • Changes in asthma-related biomarkers [ Time Frame: From Baseline to Week 12 ]
  • Change in lung epithelial cell gene expression [ Time Frame: From Baseline to Week 12 ]
  • Relative change in fractional exhaled nitric oxide (FeNO) [ Time Frame: From Baseline to Week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Evaluating the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Participants With Uncontrolled Asthma
Official Title  ICMJE A Phase II, Randomized, Double-Blind, Placebo-Controlled Bronchoscopy Study to Evaluate the Effects of Lebrikizumab on Airway Eosinophilic Inflammation in Patients With Uncontrolled Asthma on Inhaled Corticosteroids and a Second Controller Medication
Brief Summary This Phase II, randomized, double-blind, placebo-controlled, multicenter study will evaluate the effects of lebrikizumab on airway eosinophilic inflammation in participants with uncontrolled asthma who are using inhaled corticosteroid (ICS) treatment and a second controller medication. Enrolled participants will undergo a 3-week screening period during which assessments, including a bronchoscopy procedure, will be made. Participants will subsequently be randomized to receive lebrikizumab or placebo by subcutaneous (SC) injection on Day 1, Day 8, Week 4, and Week 8. Participants will continue their standard of care therapy throughout the study. End of treatment assessments will be taken at Week 12. Total study period, including screening and follow-up, is expected to last 23 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Lebrikizumab
    Lebrikizumab will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.
    Other Name: RO5490255
  • Drug: Placebo
    Lebrikizumab matching placebo will be administered by SC injection on Day 1, Day 8, Week 4, and Week 8.
  • Drug: Inhaled corticposteroids (ICS)
    Participants will continue their ICS controller therapy, as they are receiving prior to screening, throughout the study. Protocol does not specify any particular ICS.
  • Drug: Second Asthma Controller Medication
    Participants will continue their asthma controller therapy, as they are receiving prior to screening, throughout the study.
Study Arms  ICMJE
  • Experimental: Lebrikizumab
    Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab on Days 1 and 8, and on Weeks 4 and 8.
    Interventions:
    • Drug: Lebrikizumab
    • Drug: Inhaled corticposteroids (ICS)
    • Drug: Second Asthma Controller Medication
  • Placebo Comparator: Placebo
    Participants with uncontrolled asthma on ICS therapy (not specified in the protocol) and a second controller medication, will receive SC injection of lebrikizumab matching placebo on Days 1 and 8, and on Weeks 4 and 8.
    Interventions:
    • Drug: Placebo
    • Drug: Inhaled corticposteroids (ICS)
    • Drug: Second Asthma Controller Medication
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 1, 2016)
64
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2014)
120
Actual Study Completion Date  ICMJE October 13, 2016
Actual Primary Completion Date October 13, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Asthma diagnosis for greater than or equal to (>/=) 12 months prior to Visit 1
  • Bronchodilator response demonstrated within the 12 months before Visit 1 or at Visit 1, 2, or 3 of screening
  • Pre-bronchodilator FEV1 of 40 percent (%) - 80% predicted at both Visits 2 and 3
  • On ICS therapy at a total daily dose of 500-2000 mcg of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/= 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1, and no anticipated changes throughout the study
  • On an eligible second controller medication (long-acting Beta-agonist [LABA), leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonists [LAMAs] or theophylline) for 6 months prior to Visit 1, with no changes within 4 weeks prior to Visit 1, and no anticipated changes throughout the study
  • Uncontrolled asthma at Visit 1 and/or 2 and at Visit 3
  • Chest X-ray or computed tomography (CT) scan within 12 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) that confirms the absence of other clinically significant lung disease
  • Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

  • Maintenance oral corticosteroid therapy, defined as daily alternate-day oral corticosteroid maintenance therapy within 3 months prior to Visit 1
  • Treatment with systemic corticosteroids within 4 weeks prior to Visit 1 or during the screening period for any reason, including an acute exacerbation event
  • Any infection requiring hospital, intravenous (IV) or intramuscular (IM) antibiotic treatment or any respiratory infection within 4 weeks prior to Visit 1 or during screening. Any infection requiring oral antibiotic treatment with 2 weeks prior to Visit 1 or during screening, or any parasitic infection within 6 months prior to Visit 1 or during screening
  • Active tuberculosis requiring treatment within 12 months prior to Visit 1
  • Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
  • History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma
  • Known current malignancy or current evaluation for a potential malignancy
  • Unable to safely undergo elective flexible fiberoptic bronchoscopy
  • Clinically significant medical disease that is uncontrolled despite treatment, that is likely, in the opinion of the investigator, to impact the participant's ability to participate in the study, or to impact the study assessments
  • History of alcohol or drug abuse that would impair or risk the participant's full participation in the study, in the opinion of the investigator
  • Current smoker or history of smoking (greater than [>] 10 pack-years), or unwillingness to abstain from smoking for the duration of the study
  • Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
  • Use of a licensed or investigational monoclonal antibody other than anti-IL-13, or anti IL-4/IL-13, including, but not limited to, omalizumab, anti-IL-5, or anti-IL-17, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
  • Use of a systemic immunomodulatory or immunosuppressive therapy within 3 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
  • Use of other investigational therapy within 4 weeks or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
  • Initiation of or increase in allergen immunotherapy within 3 months prior to Visit 1 or during screening
  • Body mass index >38 kilograms per square meter (kg/m^2)
  • Body weight <40 kilograms (kg)
  • History of bronchial thermoplasty
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   France,   Ireland,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02099656
Other Study ID Numbers  ICMJE GB29260
2014-000275-14 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP